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metabolic syndrome X; obesity syndrome x; insulin-resistance syndrome; dysmetabolic syndrome

Characterizes individuals at risk for coronary artery disease. Etiology: - excess calorie intake - inactivity - linked to work stress [8] - financial worry, intimate partner violence, neighborhood poverty, depression [25] - intestinal flora may play a role - chemotherapy, especially combination chemotherapy [12] Epidemiology: 1) overall prevalence 24% [4,5] 2) prevalence of 44% age 60-70 3) Mexican-Americans with highest prevalence of 32% 4) male:female ratio 1 for whites, but < 1 for African-Americans & Mexican-Americans [4] Pathology: - inflammation may play a role in cardiovascular risk & risk of frailty - syndrome also occurs in primates Genetics: - implicated genes: INPPL1, ENPP1 Clinical manifestations: 1) abdominal obesity - elevated waist circumference - > 102 cm or 40 " in men, > 88 cm or 35 " in women 2) dyslipidemia (see Laboratory) 4) elevated blood pressure a) blood pressure* > 130/85 mm Hg or use of anti-hypertensive agent [12,18] b) systolic BP > 130 mm Hg or diastolic BP > 85 mm Hg 5) insulin resistance 6) waist circumference* - > 102 cm (40 inches) in men; > 88 cm (35 inches) in women - in Asian-Americans, > 89 cm (35 inches) in men or > 79 cm (31 inches) in women [12] 7) erectile dysfunction is common * defining characteristics; 3 or 4 makes diagnosis (also see Laboratory) Laboratory: 1) serum triglycerides* > 150 mg/dL or drug therapy targeting elevated serum triglycerides [12] 2) HDL cholesterol* < 40 mg/dL (men), < 50 mg/dL (women) or drug therapy targeting low HDL cholesterol [12] 3) fasting serum glucose* > 100 mg/dL or use of hypoglycemic agent [12,18] 4) elevated serum C-reactive protein is an inflammatory marker of metabolic syndrome 5) elevated 11-beta-hydroxysteroid dehydrogenase-1 in adipose tissue 6) see ARUP consult [15] * defining characteristics; 3 or 4 makes diagnosis (also see Clinical manifestations) Special laboratory: - lower scores on standardized tests of arithmetic & spelling (adolescents) [17] Radiology: - magnetic resonance imaging of brain (adolescents) - reduced hippocampal volume - increased cerebrospinal fluid volume [17] Complications: 1) increased risk of cardiovascular disease [12,18] a) risk of myocardial infarction similar to that conferred by diabetes mellitus type-2 alone [13] b) stroke [9] c) recovery from metabolic syndrome associated with reduced risk for major cardiovascular events [28] 2) increased risk of diabetes mellitus type-2 3) increased risk of frailty [21] Management: 1) intensified life-style management a) diet - multicomponent American Heart Association (AHA) diet - increasing fiber alone of benefit [22] - intermittent fasting (8-10 hours/day) may improve glycemic control & may have wider cardiometabolic benefits in adults with metabolic syndrome [29] b) exercise - moderate pace walking for 1 hour once or twice a week may be inadequate in some patients [21] - a personalized exercise program incorporating an activity tracker may help reduce the severity of metabolic syndrome [26] - see exercise 2) pharmaceutical agents a) consider statin for hyperlipidemia - cardiovascular risk further reduced with addition of fenofibrate to statin [27] (risk of rhabdomyolysis may be increased) b) consider ACE inhibitor for hypertension c) consider metformin or acarbose for hyperglycemia d) aspirin 81 mg QD if 10 year cardiovascular risk > 10% 3) treatment of obstructive sleep apnea with CPAP may improve some components of metabolic syndrome, especially hypertension [14] 4) gastric bypass 5) sirtuins, because of their induction by life-prolonging calorie restriction, may serve as potential therapeutic targets for metabolic syndrome [10] Comparative biology: - relatively large numbers of Firmicutes & small numbers of Bacteroidetes in the rats' intestine leads to glucose intolerance & obesity [24] - + Firmicutes/- Bacteroidetes is associated with high amounts of acetate in the gut & this is increased by high-fat diet - acetate is absorbed from the gut into the circulation & crosses the blood-brain barrier into the brain - within the brain, acetate stimulates the parasympathetic nervous system to increase pancreatic beta-cell production of insulin in response to gluxose & increases production of ghrelin in the stomach - elimination of gut bacteria with antibiotics, vagotomy or administration of atropine revereses effect [24]

Interactions

disease interactions

Related

11-beta hydroxysteroid dehydrogenase-1 (corticosteroid 11-beta-dehydrogenase isozyme 1, 11-DH, 11-beta-HSD1, HSD11B1, HSD11, HSD11L) diabetes mellitus hypertension (HTN, high blood pressure, HBP) hypertriglyceridemia obesity

Specific

cardiovascular-kidney-metabolic (CKM) syndrome

General

chronic metabolic disease syndrome

Database Correlations

OMIM 125853

References

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  2. Journal Watch 21(11):86, 2001
  3. Journal Watch 22(2):13, 2002
  4. Journal Watch 22(4):28, 2002 Ford et al, JAMA 287:356, 2002
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  6. Internal Medicine News 20(8)2005 cites R Shabsigh & data from the Massachussets Male Aging Study
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  10. Guarente L. Sirtuins as potential targets for metabolic syndrome. Nature. 2006 Dec 14;444(7121):868-74. Review. PMID: 17167475
  11. Prescriber's Letter 15(6): 2008 Metabolic Syndrome in Children and Adolescents Detail-Document#: 240612 (subscription needed) http://www.prescribersletter.com
  12. Medical Knowledge Self Assessment Program (MKSAP) 15, 16, 17 American College of Physicians, Philadelphia 2009, 2012, 2015
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  14. Sharma SK et al CPAP for the Metabolic Syndrome in Patients with Obstructive Sleep Apnea N Engl J Med 2011; 365:2277-2286 PMID: 22168642 http://www.nejm.org/doi/full/10.1056/NEJMoa1103944
  15. ARUP Consult: Metabolic Syndrome The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/metabolic-syndrome
  16. Carnethon MR et al Association of Weight Status With Mortality in Adults With Incident Diabetes JAMA. 2012;308(6):581-590 PMID: 22871870 http://jama.jamanetwork.com/article.aspx?articleid=1309174 - Florez H and Castillo-Florez S Beyond the Obesity Paradox in Diabetes: Fitness, Fatness, and Mortality JAMA. 2012;308(6):619-620 PMID: 22871873 http://jama.jamanetwork.com/article.aspx?articleid=1309157
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  19. Blaha MJ, Bansal S, Rouf R et al A practical "ABCDE" approach to the metabolic syndrome. Mayo Clin Proc. 2008 Aug;83(8):932-41. PMID: 18674478
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  21. Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013
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  24. Perry RJ et al. Acetate mediates a microbiome-brain-beta-cell axis to promote metabolic syndrome. Nature 2016 Jun 9; 534:213. PMID: 27279214 - Trajkovski M, Wollheim CB. Microbial signals to the brain control weight. Nature 2016 Jun 9; 534:185 PMID: 27279209
  25. Pantell MS, Prather AA, Downing JM, Gordon NP, Adler NE. Association of social and behavioral risk factors with earlier onset of adult hypertension and diabetes. JAMA Netw Open 2019 May 3; 2:e193933. PMID: 31099868 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2733431
  26. Haufe S, Kerling A, Protte G et al Telemonitoring-supported exercise training, metabolic syndrome severity, and work ability in company employees: a randomised controlled trial. Lancet Public Health. June 13, 2019 PMID: 31204284 Free Article https://www.thelancet.com/journals/lanpub/article/PIIS2468-2667(19)30075-1/fulltext
  27. Kim NH, Han KH, Choi J, Lee J, Kim SG. Use of fenofibrate on cardiovascular outcomes in statin users with metabolic syndrome: Propensity matched cohort study. BMJ 2019 Sep 27; 366:l5125. PMID: 31562117 Free PMC Article https://www.bmj.com/content/366/bmj.l5125
  28. Park S, Lee S, Kim Y et al Altered Risk for Cardiovascular Events With Changes in the Metabolic Syndrome Status: A Nationwide Population-Based Study of Approximately 10 Million Persons. Ann Intern Med. 2019. Nov 26. PMID: 31766057 https://annals.org/aim/article-abstract/2756142/altered-risk-cardiovascular-events-changes-metabolic-syndrome-status-nationwide-population
  29. Manoogian ENC, Wilkinson MJ, O'Neal M et al Time-Restricted Eating in Adults With Metabolic Syndrome: A Randomized Controlled Trial. Ann Intern Med. 2024. Oct 1. PMID: 39348690 https://www.acpjournals.org/doi/10.7326/M24-0859 - Manoogian EN, Chow LS, Taub PR, et al. Time-restricted eating for the prevention and management of metabolic diseases. Endocr Rev. 2022;43:405-436 PMID: 34550357 PMCID: PMC8905332 Free PMC article